Role of interleukin-4 (IL-4), IL-12, and gamma interferon in primary and vaccine-primed immune responses to Friend retrovirus infection

The immunological resistance of a host to viral infections may be strongly influenced by cytokines such as interleukin-12 (IL-12) and gamma interferon (IFN-gamma), which promote T helper type I responses, and IL-4, which prom otes T helper type 2 responses. We studied the role of these cytokines duri ng primary and secondary immune responses against Friend retrovirus infecti ons in mice. IL-4- and IL-12-deficient mice were comparable to wild-type B6 mice in the ability to control acute and persistent Friend virus infection s. In contrast, more than one-third of the IFN-gamma -deficient mice were u nable to maintain long-term control of Friend virus and developed gross spl enomegaly with high virus loads. Immunization with a live attenuated vaccin e virus prior to challenge protected all three types of cytokine-deficient mice from viremia and high levels of spleen virus despite the finding that the vaccinated IFN-gamma -deficient mice were unable to class switch from i mmunoglobulin hi (IgM) to IgG virus-neutralizing antibodies. The results in dicate that IFN-gamma plays an important role during primary immune respons es against Friend virus but is dispensable during vaccine-primed secondary responses.